UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Valproic Acid and the Antidote

Keywords: valproic acid, carnitine, ammonia (PubMed Search)

Posted: 7/15/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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Valproic Acid (Depakote) is a drug that uniquely has the ability to raise serum ammonia concentrations. It is able to do this without raising liver er enzymes and it can occur in overdose or at therapeutic levels. Do not think of this in the context of hepatic encephalopathy. This a metabolic derangement caused by VPA.

  • Any patient with somnolence, lethargy, decreased responsiveness - order a serum ammonia level as well as Valproic acid level
  • If the serum ammonia is elevated in conjunction with altered mental status consider a trial of carnitine
  • L-carnitine is a safe drug that is used in nutritional supplementation. VPA and other anticonvulsants cause carnitine deficiency
  • Most effective dose is unknown but from a recent review: IV 100 mg/kg once, followed by infusions of 50 mg/kg (to a maximum of 3 g per dose) every 8 hours until patient improves, ammonia decreases

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Category: Toxicology

Title: Toxin-Induced Bradycardia with Hypotension

Keywords: bradycardia, hypotension, beta blocker, calcium channel blocker, clonidine (PubMed Search)

Posted: 7/7/2010 by Bryan Hayes, PharmD (Emailed: 7/8/2010) (Updated: 9/23/2023)
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In a patient with toxin-induced bradycardia and hypotension, here is a quick differential to help identify the responsible substance:

  • Beta blockers
  • Calcium channel blockers
  • Cholinergics
  • Clonidine (and other alpha-2 agonists)
  • Digoxin (and other cardiac glycosides)
  • Opioids
  • Sedative hypnotics (such as benzodiazepines and barbiturates)

Less commonly seen causes include: magnesium, propafenone, and plant toxins (aconitine, andromedotoxin, veratrine).


Category: Toxicology

Title: Copperhead Snakebite

Keywords: copperhead, crofab (PubMed Search)

Posted: 6/24/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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In the state of Maryland, the most common venomous snake is the copperhead. Though not as dangerous as the rattlesnake, it can still cause loss of function of limb and mortality in the pediatric patient.

Treatment has involved the use of CroFab (Protherics, Atlanta). This ovine derived monovalent immunoglobolin is actually made against the following snakes:

  • Eastern diamondback rattlesnake
  • Western diamondback rattlesnake
  • Mojave rattlsnake
  • Cottonmouth (Water moccasin)

Though efficacy has been shown with these snakes, we are hoping for cross-reactivity when we treat copperheads. There are case series and case reports (1) that have shown anectdotal improvement. We are still awaiting a real randomized controlled trial - may never happen.

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Category: Toxicology

Title: Physostigmine for Anticholinergic Poisoning

Keywords: physostigmine, anticholinergic (PubMed Search)

Posted: 6/10/2010 by Bryan Hayes, PharmD (Updated: 9/23/2023)
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Physostigmine has been used extensively in the fields of anesthesiology and emergency medicine.  The only use of physostigmine with sound scientific support is for the management of patients with an anticholinergic syndrome, particularly those without cardiovascular compromise who have an agitated delirium.  In this population, physostigmine has an excellent risk-to-benefit profile.

  • Try benzodiazepines first.  They last longer and may diminish the need for physostigmine.
  • Obtain ECG.  If there are signs of sodium channel blockade (QRS prolongation), do not use physostigmine.
  • Administer 1-2 mg via slow IV push/infusion over at least 5 minutes.
  • Have atropine available at the bedside.
  • Effects last about 1 hour.

Category: Toxicology

Title: Deadly in a Single Dose

Keywords: pediatrics, toxicology, antidepressant, antimalarial, antipsychotic, calcium channel, aspirin (PubMed Search)

Posted: 6/4/2010 by Ellen Lemkin, MD, PharmD (Updated: 9/23/2023)
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There are a several classes of medications that can kill a toddler with a single dose. Toddlers are particularly susceptible due to their low weights and propensity to place everything in their mouths.


1. Calcium channel blockers
2. Camphor-containing rubs
3. Opioids/opiates
4. Oil of wintergreen/ aspirin
5. Cyclic antidepressants
6. Topical blood pressure patches (clonidine)
7. Eye drops and nasal sprays (oxymetazoline)
8. Sulfonylureas
9. Antimalarial drugs (cloroquine)

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Category: Toxicology

Title: Scombroid

Keywords: scombroid, seafood (PubMed Search)

Posted: 5/27/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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Scombroid is caused by ingestion of preformed histamine on skin of fish.

  • Naturally occurring histidine on scaly fish converted to histamine by surface bacteria - often fish left out too long, refrigeration will prevent the conversion.
  • Bacteria responsible are Morganelli morganii and K. pneumoniae
  • Fish: tuna, mahi mahi, amberjack, bonito, mackerel, albacore
  • Fish usually appears normal though meat may tast peppery
  • Patient presents minutes/hrs flushed, urticaria, HA, N/V
  • Self-limited and improve within hrs even without treatment
  • Antihistamines and rarley epinephrine will be needed

Category: Toxicology

Title: The "Other" Sodium Channel Blocking Agents

Keywords: sodium channel block, tricyclic antidepressant, cocaine, QRS (PubMed Search)

Posted: 5/13/2010 by Bryan Hayes, PharmD (Updated: 9/23/2023)
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We are all familiar with the classic ECG abnormalities caused by the sodium channel blocking properties of tricyclic antidepressants (QRS interval widening, R wave in aVR, S wave in I and aVL, and rightward deviation in terminal 40 msec of QRS). Here are some other medications that also block cardiac sodium channels in a similar manner:

  • Cocaine
  • Diphenhydramine
  • Cyclobenzaprine (Flexeril)
  • Carbamazepine (Tegretol)
  • Phenothiazines
  • Propoxyphene
  • Class 1A antidysrhythmics (quinidine, procainamide, disopyramide)
  • Class 1C antidysrhythmics (encainide, flecainide, propafenone, moricizine)
  • Amantadine

Category: Toxicology

Title: PRODUCT RECALL: Tylenol, Zyrtec and Motrin liquid

Keywords: Product recall, tylenol, zyrtec, motrin, pediatric, acetaminophen, ibuprofen, certirizine (PubMed Search)

Posted: 5/6/2010 by Ellen Lemkin, MD, PharmD (Updated: 9/23/2023)
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It is likely that you will be asked questions about the huge recall by McNeil..

It stems from complaints received of black particles found in the pediatric liquid formulation, which are manufactured at one facility in Fort Washington, PA.  The FDA inspected the plant and found inadequate quality standard testing and facilities. Either there were potential bacteria in one of the raw products (which did not make it to the final product), or the final concentrations were stronger than specified.

McNeil recalled forty-three formulations of pediatric liquid tylenol, zyrtec, motrin and benadryl. Generic versions are unaffected.

Complete recall information:

www.mcneilproductrecall.com

For more information and links:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210442.htm


Category: Toxicology

Title: Drug-Induced Thrombocytopenia

Keywords: heparin, cimetidine, thrombocytopenia (PubMed Search)

Posted: 4/22/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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Here are is a list of common drugs that will cause thrombocytopenia as a result of antiplatelet antibodies (its not just heparin!). This list is not complete but are common ones that you will see in the ED, coming from USH or on the floors/units during residency:

Abciximab, Acetaminophen, amiodarone, amphotericin B, ASA

Carbamazepine, cimetidine

Digoxin

Methyldopa

Quinidine, Quinine

Rifampin

Trimethoprin-sulfamethoxazole

Vancomycin


Category: Toxicology

Title: Radiopaque Drugs on AxR

Keywords: iron, metals (PubMed Search)

Posted: 4/15/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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Several drugs and compounds may be radiopaque on an abdominal radiograph. This may be helpful in an overdose to determine ingestion or amount ingested. Attached is a pic a patient that ingested potassium sustained release tables.

The mneumonic CHIPES will help you remember which are:

C - Calcium Carbonate, chloral hydrate

H - Heavy metal - like Mercury, lead

I - Iron and Iodine

P - Phenothiazines (compound that has S(C6H4)2NH in it), drugs that include: antipsychotics like chlorpromazine (thorazine) and antiemetics like prochlorperazine (compazine)

E - Enteric coated pills

S - Solvents [halogenated ones like chloroform] and Sustained Release preparations [Lithobid and K-Dur]


Attachments

KCl_patient_1.JPG (182 Kb)


Category: Toxicology

Title: Toxin-Induced Nystagmus

Keywords: nystagmus, pcp, phenytoin (PubMed Search)

Posted: 4/8/2010 by Bryan Hayes, PharmD (Updated: 4/11/2010)
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Many drugs/toxins cause nystagmus, particularly in overdose.  Vertical, horizontal, or rotary nystagmus may be noted.

The most common drug/toxin overdoses that cause nystagmus are the following:

  • Anticonvulsants (phenytoin, carbamazepine, valproic acid, lamotrigine, topiramate)
  • Ethanol
  • Lithium
  • Dextromethorphan
  • Phencyclidine (PCP)
  • Ketamine
  • Lysergic acid diethylamide (LSD)

Category: Toxicology

Title: N-acetylcysteine

Keywords: acetaminophen; acetylcysteine (PubMed Search)

Posted: 4/2/2010 by Ellen Lemkin, MD, PharmD (Updated: 9/23/2023)
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Recently, a toxicoeconomic study was done to compare length of stay and costs of hospitalization of a group who received
IV n-acetylcysteine (n=191) to those received oral n-acetylcysteine (n=70) prior to the availability of the intravenous formulation.
 
What they found was that patients treated with IV acetylcysteine had a decreased length of stay (4 days vs 7 days, p< 0.001) and cost of hospitalization ($7,607 vs $18,287,  p<0.001) compared to the enteral group.
 
 

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Category: Toxicology

Title: Tox Screen - The False Positives

Keywords: urine toxicology screen (PubMed Search)

Posted: 3/18/2010 by Fermin Barrueto, MD (Updated: 3/27/2010)
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When you draw a urine toxicology screen it can mislead more often than help you. Here is a quick list of the test followed by some medications that cause false positives - when in doubt, call your lab to find out specifics since results will vary lab to lab:

TCA - diphenhydramine, carbamazepine, cyclobenzaprine (side note: TCA screen should never be used to determine TCA toxicity, your ECG and physical exam should be enough to determine if the patient is toxic from TCA

Cocaine - the most accurate test on the screen, positive for up to 5 days

PCP - dextromethorphan and ketamine can turn it positive

Amphetamines - pseudoephedrine, ephedrine, phenylephrine and many other OTC cough decongestants can as well, the worst screening test with the largest number of false positives


Category: Toxicology

Title: Food allergy cross-reactivity

Keywords: food, allergy, propofol, soy, peanut, egg (PubMed Search)

Posted: 3/9/2010 by Bryan Hayes, PharmD (Emailed: 3/11/2010) (Updated: 3/20/2010)
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According to the Food Allergy and Anaphylaxis Network, the eight most common food allergies, which account for 90% of the food allergies in the U.S., are: dairy, soy, wheat, shellfish, fish, peanut, tree nut, and egg.

Several medications are formulated with these ingredients and should be avoided in patients with reported allergies.

  • Propofol is a lipid emulsion that contains egg.  Avoid in patient with hypersensitivity to eggs, egg products, soybeans, or soy products.
  • Ipratropium ± albuterol (Atrovent, Combvient®) inhalers may contain soy lecithin.  This can cause allergic reactions in patients with allergy to soy lecithin or related food products (e.g., soybean and peanut).  Nebulizer solutions (e.g., Duoneb®) seem to be free from this issue.
  • Progesterone (Prometrium®) capsules contain peanut oil.

Category: Toxicology

Title: Cutting Edge vs. Old School for Overdoses

Keywords: Lavage, activated charcoal, hyperinsulinemia, intralipid, toxicology, narcan (PubMed Search)

Posted: 3/4/2010 by Ellen Lemkin, MD, PharmD (Updated: 9/23/2023)
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Cutting Edge
Old School
  Gastric Lavage
Hyperinsulinemia and Euglycemia Supportive care, glucagon for beta blocker overdoses
Intralipid administration Supportive care for anesthetic overdoses, TCAs, and other lipid soluble agents
Low dose or NO narcan High dose narcan for opoid overdoses
Checking salicylates and tylenol levels for overdose Tox screens for everyone

Category: Toxicology

Title: Rodenticides

Keywords: cholecalciferol, brodifacoum (PubMed Search)

Posted: 2/18/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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When a child is reported to be exposed to a rat poison it is commonly a long acting coumarin like brodifacoum. The rat usually eats the poison then during its traumatic little life will cause its own death by jumping and squeezing through a crack. When a human is exposed, this is the typical sequence of events:

  1. Exposure (and when you usually see them in the ED)
  2. 24-72 hrs later you will actually see an INR rise if actually ingested

Treatment is the same as for coumadin, vitamin K. However, do not start empirically since the patient will be committed to high doses of vitamin K for several months. Let the patient prove they have been poisoned which means they will require recheck of their INR 2-3 days later though they can be sent home with specific warning signs of anticoagulation.


Category: Toxicology

Title: Transplant Med Toxicology

Keywords: transplant, tacrolimus, sirolimus, cyclosporine (PubMed Search)

Posted: 2/9/2010 by Bryan Hayes, PharmD (Emailed: 2/11/2010) (Updated: 2/11/2010)
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With all of the post-transplant patients we see in the ED, a refresher on the toxicities associated with the most common immunosuppressant medications is warranted.

 

Cyclosporine (Sandimmune® and Neoral®/Gengraf®) and tacrolimus (Prograf®) are both calcineurin inhibitors that inhibit activation and proliferation of T-lymphocytes and IL-2.

-          Major concerns: Nephrotoxicity, drug interactions (CYP3A4)

-          Adverse Effects:

o       Electrolyte abnormalities: ­K+, ¯Mg+, ­glucose

o       CNS: HA, tremor (statistically higher with tacrolimus)

o       CV: HTN, ­ lipids (increased with cyclosporine)

o       End organ: hepatotoxicity, nephrotoxicity

o       Cosmetic (cyclosporine specific): hirsutism, gingival hyperplasia, acne

 

Sirolimus/Rapamycin (Rapamune®) is an M-tor inhibitor that inhibits T-lymphocyte activation and proliferation.

-          Major concerns: Drug interactions (CYP3A4)

-          Adverse Effects:

o       Delayed wound healing

o       Leucopenia, thrombocytopenia

o       Hypercholesterolemia


Category: Toxicology

Title: Broad spectrum antibiotics for multidrug resistant bacteria

Keywords: antibiotics, imipenem, meropenem, doripenem, ertapenem, colistin, amikacin, multiresistant (PubMed Search)

Posted: 2/4/2010 by Ellen Lemkin, MD, PharmD
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CARBAPENENEMS

  • Broadest spectrum of activity of all classes
  • Imipenem has slightly better gm + activity; lowers seizure threshold
  • Meropenem has slightly better gm - activity
  • Ertapenem does not cover Pseudomonas
  • Doripenem has the most activity against Pseudomonas
  • May use in PCN allergic patients (cross reactivity lower than previously thought)

TIGECYCLINE

  • Has broad coverage, but does not cover Pseudomonas
  • Bacteriostatic; derivative of tetracycline
  • Does NOT require renal dosing
  • Higher mortality in VAP than other agents; do not use for intra-abdominal infections (poss higher risk of perforation)

AMIKACIN

  • Has antipseudomonal activity
  • Used in combination with other agents for MDR (multi-drug resistant) bacteria
  • Causes nephrotoxicity and ototoxicity

COLISTIN

  • Bacteriocidal against many MDR gram - bacteria
  • Not active against Proteus, Provincia, Burkholderia, Neisseria, or Serratia
  • Nephrotoxicity and ototoxicity reported

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Category: Toxicology

Title: RCIN Continued

Keywords: saline, sodium bicarbonate, acetylcystein (PubMed Search)

Posted: 1/28/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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Apologies - last few bullets were cutoff - Continuing - Prophylaxis against RCIN has been attempted with the following:

  • IV saline infusion
  • Sodium Bicarbonate bolus
  • IV acetylcysteine infusion

No one therapy has been show to have superior efficacy.


Category: Toxicology

Title: Radiocontrast Induced Nephropathy

Keywords: RCIN, renal failure (PubMed Search)

Posted: 1/28/2010 by Fermin Barrueto, MD (Updated: 9/23/2023)
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Radiocontrast Induced Nephropathy (RCIN)

  • Occurs within 24 hrs of administration followed by oliguric phase
  • Usually improves within a week and rarely needs dialysis
  • Initial injection is an osmotic load, leads to volume expansion and diuresis. Follwed by intense vasoconstriction suggesting possible ischemic role in pathophysiology.
  • There is also a direct toxic effect to the kidneys however
  • High Risk patients: HTN, DM,  Chronic Renal Insuff, Bence Jones proteinuria and large injections of IV dye
  • Possible prophylaxis: There is almost no data studying this effect in the Emerg Dept patient. One trial look at IV acetylcysteine in the Emergent CT (RAPPID trial) did show benefit but has flaws within the study. IV hydration and sodium bicarbonate

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